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Nat Genet DOI:10.1038/ng.233

Common variants at CD40 and other loci confer risk of rheumatoid arthritis.

Publication TypeJournal Article
Year of Publication2008
AuthorsRaychaudhuri, S, Remmers, EF, Lee, AT, Hackett, R, Guiducci, C, Burtt, NP, Gianniny, L, Korman, BD, Padyukov, L, Kurreeman, FAS, Chang, M, Catanese, JJ, Ding, B, Wong, S, van Mil, AHM van de, Neale, BM, Coblyn, J, Cui, J, Tak, PP, Wolbink, GJan, J Crusius, BA, van der Horst-Bruinsma, IE, Criswell, LA, Amos, CI, Seldin, MF, Kastner, DL, Ardlie, KG, Alfredsson, L, Costenbader, KH, Altshuler, D, Huizinga, TWJ, Shadick, NA, Weinblatt, ME, de Vries, N, Worthington, J, Seielstad, M, Toes, REM, Karlson, EW, Begovich, AB, Klareskog, L, Gregersen, PK, Daly, MJ, Plenge, RM
JournalNat Genet
Volume40
Issue10
Pages1216-23
Date Published2008 Oct
ISSN1546-1718
KeywordsAntigens, CD40, Arthritis, Rheumatoid, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Genetic Linkage, Genetic Predisposition to Disease, Genome, Human, Haplotypes, Humans, Polymorphism, Single Nucleotide
Abstract

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).

URLhttp://dx.doi.org/10.1038/ng.233
DOI10.1038/ng.233
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/18794853?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID18794853
PubMed Central IDPMC2757650
Grant ListR01 AR044422-10 / AR / NIAMS NIH HHS / United States
M01 RR000079 / RR / NCRR NIH HHS / United States
R01-AR44422 / AR / NIAMS NIH HHS / United States
5 M01 RR-00079 / RR / NCRR NIH HHS / United States
K24 AR0524-01 / AR / NIAMS NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
R01 AR044422 / AR / NIAMS NIH HHS / United States
U01 HG004171 / HG / NHGRI NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
K08 AR055688-01A1 / AR / NIAMS NIH HHS / United States
17552 / / Arthritis Research UK / United Kingdom
R01 AI065841 / AI / NIAID NIH HHS / United States
K08 KAR055688A / / PHS HHS / United States
P60 AR047782 / AR / NIAMS NIH HHS / United States
T32 AR007530 / AR / NIAMS NIH HHS / United States
R01 AR49880 / AR / NIAMS NIH HHS / United States
K24 AR02175 / AR / NIAMS NIH HHS / United States
R01 AR049880 / AR / NIAMS NIH HHS / United States
/ / Arthritis Research UK / United Kingdom
UO1 HG004171 / HG / NHGRI NIH HHS / United States
N01-AR-2-2263 / AR / NIAMS NIH HHS / United States
Z01 AR041139-05 / / Intramural NIH HHS / United States
AR007530-23 / AR / NIAMS NIH HHS / United States
K08 AR055688 / AR / NIAMS NIH HHS / United States
K12 HD051959 / HD / NICHD NIH HHS / United States
K24 AR002175 / AR / NIAMS NIH HHS / United States
K08 AI055314 / AI / NIAID NIH HHS / United States
R01 AR044422-09A1 / AR / NIAMS NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
K08 AI55314-3 / AI / NIAID NIH HHS / United States